Perinatal Acetaminophen Exposure and Childhood Attention-Deficit/Hyperactivity Disorder (ADHD): Exploring the Role of Umbilical Cord Plasma Metabolites in Oxidative Stress Pathways
| dc.contributor.author | Anand, Neha S. | en |
| dc.contributor.author | Raghavan, Ramkripa | en |
| dc.contributor.author | Wang, Guoying | en |
| dc.contributor.author | Hong, Xiumei | en |
| dc.contributor.author | Azuine, Romuladus E. | en |
| dc.contributor.author | Pearson, Colleen | en |
| dc.contributor.author | Zuckerman, Barry | en |
| dc.contributor.author | Xie, Hehuang | en |
| dc.contributor.author | Wang, Xiaobin | en |
| dc.date.accessioned | 2021-10-13T12:27:47Z | en |
| dc.date.available | 2021-10-13T12:27:47Z | en |
| dc.date.issued | 2021-09-30 | en |
| dc.date.updated | 2021-10-12T14:18:12Z | en |
| dc.description.abstract | Oxidative stress mechanisms may explain associations between perinatal acetaminophen exposure and childhood attention-deficit hyperactivity disorder (ADHD). We investigated whether the changes in umbilical cord plasma amino acids needed to synthesize the antioxidant glutathione and in the oxidative stress biomarker 8-hydroxy-deoxyguanosine may explain the association between cord plasma acetaminophen and ADHD in the Boston Birth Cohort (BBC). Mother–child dyads were followed at the Boston Medical Center between 1998 and 2018. Cord plasma analytes were measured from archived samples collected at birth. Physician diagnoses of childhood ADHD were obtained from medical records. The final sample consisted of 568 participants (child mean age [SD]: 9.3 [3.5] years, 315 (52.8%) male, 248 (43.7%) ADHD, 320 (56.3%) neurotypical development). Cord unmetabolized acetaminophen was positively correlated with methionine (R = 0.33, <i>p</i> < 0.001), serine (R = 0.30, <i>p</i> < 0.001), glycine (R = 0.34, <i>p</i> < 0.001), and glutamate (R = 0.16, <i>p</i> < 0.001). Children with cord acetaminophen levels >50th percentile appeared to have higher risk of ADHD for each increase in cord 8-hydroxy-deoxyguanosine level. Adjusting for covariates, increasing cord methionine, glycine, serine, and 8-hydroxy-deoxyguanosine were associated with significantly higher odds for childhood ADHD. Cord methionine statistically mediated 22.1% (natural indirect effect logOR = 0.167, SE = 0.071, <i>p</i> = 0.019) and glycine mediated 22.0% (natural indirect effect logOR = 0.166, SE = 0.078, <i>p</i> = 0.032) of the association between cord acetaminophen >50th percentile with ADHD. Our findings provide some clues, but additional investigation into oxidative stress pathways and the association of acetaminophen exposure and childhood ADHD is warranted. | en |
| dc.description.version | Published version | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.citation | Anand, N.S.; Raghavan, R.; Wang, G.; Hong, X.; Azuine, R.E.; Pearson, C.; Zuckerman, B.; Xie, H.; Wang, X. Perinatal Acetaminophen Exposure and Childhood Attention-Deficit/Hyperactivity Disorder (ADHD): Exploring the Role of Umbilical Cord Plasma Metabolites in Oxidative Stress Pathways. Brain Sci. 2021, 11, 1302. | en |
| dc.identifier.doi | https://doi.org/10.3390/brainsci11101302 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/105274 | en |
| dc.language.iso | en | en |
| dc.publisher | MDPI | en |
| dc.rights | Creative Commons Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.subject | ADHD | en |
| dc.subject | cord blood | en |
| dc.subject | acetaminophen | en |
| dc.subject | glutathione | en |
| dc.subject | oxidative stress | en |
| dc.subject | neurodevelopment | en |
| dc.title | Perinatal Acetaminophen Exposure and Childhood Attention-Deficit/Hyperactivity Disorder (ADHD): Exploring the Role of Umbilical Cord Plasma Metabolites in Oxidative Stress Pathways | en |
| dc.title.serial | Brain Science | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |